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PMID: 10341237 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The mitogen-activated protein kinase cascade couples PKA and PKC to cAMP response element binding protein phosphorylation in area CA1 of hippocampus.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 19 ·No. 11 ·1999-06-01 ·Pages 4337-48

Roberson ED, English JD, Adams JP, Selcher JC, Kondratick C, Sweatt JD

Abstract

Activation of the mitogen-activated protein kinase (MAPK) cascade recently was discovered to play an important role in synaptic plasticity in area CA1 of rat hippocampus. However, the upstream mechanisms regulating MAPK activity and the downstream effectors of MAPK in the hippocampus are uncharacterized. In the present studies we observed that hippocampal MAPK activation is regulated by both the PKA and PKC systems; moreover, we found that a wide variety of neuromodulatory neurotransmitter receptors (metabotropic glutamate receptors, muscarinic acetylcholine receptors, dopamine receptors, and beta-adrenergic receptors) couple to MAPK activation via these two cascades. In additional studies we observed that PKC is a powerful regulator of CREB phosphorylation in area CA1. MAPK plays a critical role in transcriptional regulation by PKC, because MAPK activation is a necessary component for increased CREB phosphorylation in response to the activation of this kinase. Surprisingly, we also observed that MAPK activation is necessary for PKA coupling to CREB phosphorylation in area CA1. Overall, these studies indicate an unexpected richness of diversity in the regulation of MAPK in the hippocampus and suggest the possibility of a broad role for the MAPK cascade in regulating gene expression in long-term forms of hippocampal synaptic plasticity.

MeSH Terms
Animals Calcium-Calmodulin-Dependent Protein Kinases/metabolism Cyclic AMP Response Element-Binding Protein/metabolism Cyclic AMP-Dependent Protein Kinases/metabolism Hippocampus/metabolism In Vitro Techniques Male Nerve Tissue Proteins/metabolism Phosphorylation Protein Kinase C/metabolism Rats Rats, Sprague-Dawley Receptors, Adrenergic, beta/physiology Receptors, Dopamine/physiology Receptors, Metabotropic Glutamate/physiology Receptors, Muscarinic/physiology Signal Transduction/physiology
Chemicals
Cyclic AMP Response Element-Binding Protein Nerve Tissue Proteins Receptors, Adrenergic, beta Receptors, Dopamine Receptors, Metabotropic Glutamate Receptors, Muscarinic Cyclic AMP-Dependent Protein Kinases Protein Kinase C Calcium-Calmodulin-Dependent Protein Kinases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Roberson E D
Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA.
English J D
Adams J P
Selcher J C
Kondratick C
Sweatt J D
References (50)
50 references, click to expand
  1. Cellular mechanisms of noradrenergic enhancement of long-term synaptic potentiation in hippocampus.
    NIDA Res Monogr. 1987;78:95-107 PMID: 3123992
  2. cAMP activates MAP kinase and Elk-1 through a B-Raf- and Rap1-dependent pathway.
    Cell. 1997 Apr 4;89(1):73-82 PMID: 9094716
  3. Persistent protein kinase activation in the maintenance phase of long-term potentiation.
    J Biol Chem. 1991 Dec 25;266(36):24253-6 PMID: 1684790
  4. Transient activation of cyclic AMP-dependent protein kinase during hippocampal long-term potentiation.
    J Biol Chem. 1996 Nov 29;271(48):30436-41 PMID: 8940008
  5. Characterisation of LTP induced by the activation of glutamate metabotropic receptors in area CA1 of the hippocampus.
    Neuropharmacology. 1993 Jan;32(1):1-9 PMID: 8381524
  6. Coupling of the RAS-MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase.
    Science. 1996 Aug 16;273(5277):959-63 PMID: 8688081
  7. Identification of a novel inhibitor of mitogen-activated protein kinase kinase.
    J Biol Chem. 1998 Jul 17;273(29):18623-32 PMID: 9660836
  8. Persistent activation of the zeta isoform of protein kinase C in the maintenance of long-term potentiation.
    Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8342-6 PMID: 8378304
  9. A family of cAMP-binding proteins that directly activate Rap1.
    Science. 1998 Dec 18;282(5397):2275-9 PMID: 9856955
  10. How MAP kinases are regulated.
    J Biol Chem. 1995 Jun 23;270(25):14843-6 PMID: 7797459
  11. A protein kinase C-, Ras-, and RSK2-dependent signal transduction pathway activates the cAMP-responsive element-binding protein transcription factor following T cell receptor engagement.
    J Biol Chem. 1998 Aug 28;273(35):22841-7 PMID: 9712919
  12. Identification of regulatory phosphorylation sites in mitogen-activated protein kinase (MAPK)-activated protein kinase-1a/p90rsk that are inducible by MAPK.
    J Biol Chem. 1998 Jan 16;273(3):1496-505 PMID: 9430688
  13. Effects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons.
    Science. 1993 Jun 11;260(5114):1661-4 PMID: 8389057
  14. A requirement for the mitogen-activated protein kinase cascade in hippocampal long term potentiation.
    J Biol Chem. 1997 Aug 1;272(31):19103-6 PMID: 9235897
  15. A biochemist's view of long-term potentiation.
    Learn Mem. 1996 Jul-Aug;3(1):1-24 PMID: 10456072
  16. Protein kinase C mediates activation of nuclear cAMP response element-binding protein (CREB) in B lymphocytes stimulated through surface Ig.
    J Immunol. 1995 Feb 15;154(4):1717-23 PMID: 7836756
  17. Multiple and cooperative phosphorylation events regulate the CREM activator function.
    EMBO J. 1993 Oct;12(10):3903-11 PMID: 8404858
  18. Multiple protein kinase A-regulated events are required for transcriptional induction by cAMP.
    Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10521-5 PMID: 7479832
  19. cAMP response element-binding protein is activated by Ca2+/calmodulin- as well as cAMP-dependent protein kinase.
    Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):5061-5 PMID: 1647024
  20. Activation of p42 mitogen-activated protein kinase in hippocampal long term potentiation.
    J Biol Chem. 1996 Oct 4;271(40):24329-32 PMID: 8798683
  21. Polymyxin B, an inhibitor of protein kinase C, prevents the maintenance of synaptic long-term potentiation in hippocampal CA1 neurons.
    Brain Res. 1988 Feb 9;440(2):305-14 PMID: 2833996
  22. nMDA receptor activation increases cyclic AMP in area CA1 of the hippocampus via calcium/calmodulin stimulation of adenylyl cyclase.
    J Neurochem. 1993 Nov;61(5):1933-42 PMID: 7901336
  23. Activity-dependent beta-adrenergic modulation of low frequency stimulation induced LTP in the hippocampal CA1 region.
    Neuron. 1996 Sep;17(3):475-82 PMID: 8816710
  24. Noradrenergic enhancement of long-term potentiation at mossy fiber synapses in the hippocampus.
    J Neurophysiol. 1988 Feb;59(2):667-87 PMID: 2832552
  25. The MAPK cascade is required for mammalian associative learning.
    Nat Neurosci. 1998 Nov;1(7):602-9 PMID: 10196568
  26. MAP kinase translocates into the nucleus of the presynaptic cell and is required for long-term facilitation in Aplysia.
    Neuron. 1997 Jun;18(6):899-912 PMID: 9208858
  27. Induction of CRE-mediated gene expression by stimuli that generate long-lasting LTP in area CA1 of the hippocampus.
    Neuron. 1996 May;16(5):973-82 PMID: 8630255
  28. Phosphorylation of mitogen-activated protein kinase by one-trial and multi-trial classical conditioning.
    J Neurosci. 1998 May 1;18(9):3480-7 PMID: 9547255
  29. Inhibitors of calmodulin and protein kinase C block different phases of hippocampal long-term potentiation.
    Brain Res. 1988 Oct 4;461(2):388-92 PMID: 3179724
  30. The effect of dopaminergic D1 receptor blockade during tetanization on the expression of long-term potentiation in the rat CA1 region in vitro.
    Neurosci Lett. 1991 Aug 5;129(1):111-4 PMID: 1833673
  31. The alpha-bungarotoxin-binding nicotinic acetylcholine receptor from rat brain contains only the alpha7 subunit.
    J Biol Chem. 1997 Sep 19;272(38):24024-9 PMID: 9295355
  32. N-methyl-D-aspartate receptor activation increases cAMP levels and voltage-gated Ca2+ channel activity in area CA1 of hippocampus.
    Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6467-71 PMID: 1677768
  33. Signaling from synapse to nucleus: postsynaptic CREB phosphorylation during multiple forms of hippocampal synaptic plasticity.
    Neuron. 1996 Jan;16(1):89-101 PMID: 8562094
  34. Postsynaptic cAMP pathway gates early LTP in hippocampal CA1 region.
    Neuron. 1995 Dec;15(6):1403-14 PMID: 8845163
  35. Anisomycin, an inhibitor of protein synthesis, blocks late phases of LTP phenomena in the hippocampal CA1 region in vitro.
    Brain Res. 1988 Jun 14;452(1-2):57-65 PMID: 3401749
  36. Heightened synaptic plasticity of hippocampal CA1 neurons during a cholinergically induced rhythmic state.
    Nature. 1993 Aug 19;364(6439):723-5 PMID: 8355787
  37. RasGRP, a Ras guanyl nucleotide- releasing protein with calcium- and diacylglycerol-binding motifs.
    Science. 1998 May 15;280(5366):1082-6 PMID: 9582122
  38. Membrane depolarization and calcium influx stimulate MEK and MAP kinase via activation of Ras.
    Neuron. 1994 Jun;12(6):1207-21 PMID: 8011335
  39. Differential effects of protein kinase inhibitors on pre-established long-term potentiation in rat hippocampal neurons in vitro.
    Neurosci Lett. 1991 Jan 2;121(1-2):259-62 PMID: 2020382
  40. Cross talk between ERK and PKA is required for Ca2+ stimulation of CREB-dependent transcription and ERK nuclear translocation.
    Neuron. 1998 Oct;21(4):869-83 PMID: 9808472
  41. Potentiation of synaptic transmission in the hippocampus by phorbol esters.
    Nature. 1986 May 8-14;321(6066):175-7 PMID: 3010137
  42. Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP.
    Nature. 1998 Dec 3;396(6710):474-7 PMID: 9853756
  43. Stimulation of protein tyrosine phosphorylation by NMDA receptor activation.
    Science. 1991 Aug 23;253(5022):912-4 PMID: 1715095
  44. Protein kinase A inhibitors prevent the maintenance of hippocampal long-term potentiation.
    Neuroreport. 1993 Jun;4(6):712-4 PMID: 8347813
  45. Metabotropic receptor stimulation coupled to weak tetanus leads to long-term potentiation and a rapid elevation of cytosolic protein kinase C activity.
    Brain Res. 1993 Jun 4;613(1):1-9 PMID: 8348292
  46. Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein.
    Cell. 1994 Oct 7;79(1):59-68 PMID: 7923378
  47. A Rap guanine nucleotide exchange factor enriched highly in the basal ganglia.
    Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13278-83 PMID: 9789079
  48. Measuring the impact of probabilistic transmission on neuronal output.
    Neuron. 1993 Jun;10(6):1101-11 PMID: 8318231
  49. L-type voltage-sensitive Ca2+ channel activation regulates c-fos transcription at multiple levels.
    J Biol Chem. 1995 Mar 3;270(9):4224-35 PMID: 7876182
  50. Mechanism of protein kinase C activation during the induction and maintenance of long-term potentiation probed using a selective peptide substrate.
    Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8337-41 PMID: 8378303
Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
1999-06-01
Pages
4337-48
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6782591
Subset
IM
Grants
NIMH NIH HHS · R01 MH057014 · United States
NIMH NIH HHS · MH57014 · United States
External Links
PubMed source PMC Full Text View journal details
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